(4-piperidinylmethyl and -hetero) purines

Abstract

(4-Piperidinylmethyl and -hetero)purines having antihistaminic properties and being useful agents in the treatment of allergic diseases.

What we claim is: 
     
       1. A compound of the formula: ##STR52## a pharmaceutically acceptable acid addition salt or a possible stereochemically isomeric form thereof, wherein: --A 1  ═A 2  --A 3  ═A 4  -- represents a bivalent radical of the formula:   --N═CH--N═CH--                                     (a-1),     or     --CH═N--CH═N--                                     (a-2),        wherein one or two hydrogen atoms in said radicals (a-1) or (a-2) may, each independently from each other, be replaced by halo, C 1-6  alkyl, C 1-6  alkyloxy, trifluoromethyl, or hydroxy; R 1  represents a member selected from the group consisting of hydrogen, C 1-10  alkyl, C 3-6  cycloalkyl, Ar 1 , and C 1-6  alkyl substituted with one or two Ar 1  radicals;   R 2  represents a member selected from the group consisting of hydrogen and C 1-6  alkyl;   B represents NR; said R being a member selected from the group consisting of hydrogen, C 1-6  alkyl, C 3-6  cycloalkyl, (C 1-6  alkyl)carbonyl, (C 1-6  alkyloxy)carbonyl, and Ar 2  -C 1-6  alkyl; and   L represents a radical of the formula:   Ar.sup.1 --T--C.sub.s H.sub.2s --                          (b-1);        wherein s represents an integer of from 1 to 6 inclusive; and   T represents O, S, NR 3 , or a direct bond, wherein R 3  represents hydrogen, C 1-6  alkyl, or Ar 2  --C 1-6  alkyl;      wherein in the foregoing Ar 1  represents a member selected from the group consisting of phenyl, substituted phenyl, pyridinyl, mono- and di(C 1-6  alkyloxy)pyridinyl, furanyl, furanyl substituted with C 1-6  alkyl, and thiazolyl; said substituted phenyl being phenyl substituted with up to 3 substituents each independently selected from the group consisting of halo, hydroxy, nitro, cyano, trifluoromethyl, C 1-6  alkyl, C 1-6  alkyloxy, C 1-6  alkylthio, mercapto, amino, mono- and di(C 1-6  alkyl)amino; and    wherein Ar 2  represents a member selected from the group consisting of phenyl and substituted phenyl; said substituted phenyl being phenyl optionally substituted with up to three substituents each independently selected from the group consisting of halo, hydroxy, trifluoromethyl, C 1-6  alkyl, C 1-6  alkyloxy.     
     
     
       2. An anti-allergic composition comprising suitable pharmaceutical carriers and as active ingredient an anti-allergic amount of a compound of the formula: ##STR53## a pharmaceutically acceptable acid addition salt or a possible stereochemically isomeric form thereof, wherein: --A 1  ═A 2  --A 3  ═A 4  -- represents a bivalent radical of the formula:   --N═CH--N═CH--                                     (a-1),     or     --CH═N--CH═N--                                     (a-2),        wherein one or two hydrogen atoms in said radicals (a-1) or (a-2) may, each independently from each other, be replaced by halo, C 1-6  alkyl, C 1-6  alkyloxy, trifluoromethyl, or hydroxy; R 1  represents a member selected from the group consisting of hydrogen, C 1-10  alkyl, C 3-6  cycloalkyl, Ar 1 , and C 1-6  alkyl substituted with one or two Ar 1  radicals;   R 2  represents a member selected from the group consisting of hydrogen and C 1-6  alkyl;   B represents NR; said R being a member selected from the group consisting of hydrogen, C 1-6  alkyl, C 3-6  cycloalkyl, (C 1-6  alkyl)carbonyl, (C 1-6  alkyloxy)carbonyl, and Ar 2  --C 1-6  alkyl; and   L represents a radical of the formula:   Ar.sup.1 --T--C.sub.s H.sub.2s --                          (b-1);        wherein s represents an integer of from 1 to 6 inclusive; and   T represents O, S, NR 3 , or a direct bond, wherein R 3  represents hydrogen, C 1-6  alkyl, or Ar 2  --C 1-6  alkyl;      wherein in the foregoing Ar 1  represents a member selected from the group consisting of phenyl, substituted phenyl, pyridinyl, mono- and di(C 1-6  alkyloxy)pyridinyl, furanyl, furanyl substituted with C 1-6  alkyl, and thiazolyl; said substituted phenyl being phenyl substituted with up to 3 substituents each independently selected from the group consisting of halo, hydroxy, nitro, cyano, trifluoromethyl, C 1-6  alkyl, C 1-6  alkyloxy, C 1-6  alkylthio, mercapto, amino, mono- and di(C 1-6  alkyl)amino; and    wherein Ar 2  represents a member selected from the group consisting of phenyl and substituted phenyl; said substituted phenyl being phenyl optionally substituted with up to three substituents each independently selected from the group consisting of halo, hydroxy, trifluoromethyl, C 1-6  alkyl, C 1-6  alkyloxy.     
     
     
       3. A method of treating allergic diseases in warm-blooded animals suffering from the same, which method comprises the systemic administration to warm-blooded animals of an effective anti-allergic amount of a compound of the formula: ##STR54## a pharmaceutically acceptable acid addition salt or a possible stereochemically isomeric form thereof, wherein: --A 1  ═A 2  --A 3  ═A 4  -- represents a bivalent radical of the formula:   --N═CH--N═CH--                                     (a-1),     or     --CH═N--CH═N--                                     (a-2),        wherein one or two hydrogen atoms in said radicals (a-1) or (a-2) may, each independently from each other, be replaced by halo, C 1-6  alkyl, C 1-6  alkyloxy, trifluoromethyl, or hydroxy; R 1  represents a member selected from the group consisting of hydrogen, C 1-10  alkyl, C 3-6  cycloalkyl, Ar 1 , and C 1-6  alkyl substituted with one or two Ar 1  radicals;   R 2  represents a member selected from the group consisting of hydrogen and C 1-6  alkyl;   B represents NR; said R being a member selected from the group consisting of hydrogen, C 1-6  alkyl, C 3-6  cycloalkyl, (C 1-6  alkyl)carbonyl, (C 1-6  alkyloxy)carbonyl, and Ar 2  --C 1-6  alkyl; and   L represents a radical of the formula:   Ar.sup.1 --T--C.sub.2 H.sub.2s --                          (b-1);        wherein s represents an integer of from 1 to 6 inclusive; and   T represents O, S, NR 3 , or a direct bond, wherein R 3  represents hydrogen, C 1-6  alkyl, or Ar 2  --C 1-6  alkyl;      wherein in the foregoing Ar 1  represents a member selected from the group consisting of phenyl, substituted phenyl, pyridinyl, mono- and di(C 1-6  alkyloxy)pyridinyl, furanyl, furanyl substituted with C 1-6  alkyl, and thiazolyl; said substituted phenyl being phenyl substituted with up to 3 substituents each independently selected from the group consisting of halo, hydroxy, nitro, cyano, trifluoromethyl, C 1-6  alkyl, C 1-6  alkyloxy, C 1-6  alkylthio, mercapto, amino, mono- and di(C 1-6  alkyl)amino; and    wherein Ar 2  represents a member selected from the group consisting of phenyl and substituted phenyl; said substituted phenyl being phenyl optionally substituted with up to three substituents each independently selected from the group consisting of halo, hydroxy, trifluoromethyl, C 1-6  alkyl, C 1-6  alkyloxy.     
     
     
       4. A compound according to claim 1 wherein R 1  represents C 1-6  alkyl substituted with one Ar 1  radical. 
     
     
       5. An anti-allergic composition according to claim 2 wherein R 1  represents C 1-6  alkyl substituted with one Ar 1  radical. 
     
     
       6. A method according to claim 3 wherein R 1  represents C 1-6  alkyl substituted with one Ar 1  radical.